- Preparation method of tenofovir prodrug intermediate GS101
-
The invention relates to a preparation method of a tenofovir prodrug intermediate GS101, and belongs to the field of organic synthesis. The method comprises the following steps. The preparation method is mild in reaction condition, and the obtained product is good in purity and high in yield.
- -
-
Paragraph 0007-0035
(2021/09/26)
-
- Industrial synthesis method of propofovir disoproxil fumarate
-
The invention provides a preparation process of propofovir disoproxil fumarate, which is short in production period, simple to operate and suitable for industrial production, and the high-purity propofovir disoproxil fumarate is prepared by taking the propofovir disoproxil fumarate as a starting material through special phosphorus chiral atom synthesis, purification and separation. The purity of the prepared propofovir disoproxil fumarate is greater than 99.90%, the diastereoisomer is less than 0.15%, the content of other single impurities is less than 0.10%, and the method has high commercialscale production value.
- -
-
Paragraph 0043-0046
(2021/01/29)
-
- Preparation method of intermediate GS102 of tenofovir prodrug
-
The invention relates to a preparation method of an intermediate GS102 of a tenofovir prodrug. A product obtained by the method is good in purity and high in yield.
- -
-
Paragraph 0008
(2021/02/13)
-
- Preparation method of intermediate GS103 of tenofovir prodrug
-
The invention relates to a preparation method of an intermediate GS103 of a tenofovir prodrug. A product obtained by the method is good in purity and high in yield.
- -
-
Paragraph 0007
(2021/02/13)
-
- Preparation method of tenofovir alafenamide intermediate
-
The invention belongs to the technical field of medicinal chemistry, and provides a preparation method of a tenofovir alafenamide intermediate. The method comprises the following steps: reacting tenofovir serving as a raw material with an alkali or an salt of an alkali metal to a generate tenofovir alkali metal single salt, and reacting the tenofovir alkali metal single salt with triphenyl phosphite to generate a target intermediate. According to the invention, the method has the advantages of simple reaction conditions, high raw material utilization degree, high yield, high purity, reductionof the use of a large amount of organic bases, less generated waste liquid, small environmental pollution, and suitableness for industrial production.
- -
-
-
- Nucleotide phosphonate monohydrate as well as preparation method and application thereof in medicine
-
The invention relates to a monohydrate of a compound (I) and a preparation method thereof, and a composition and application thereof in preparation of drugs for treatment of viral infectious diseases.
- -
-
Paragraph 0034; 0038; 0049-0054
(2020/03/17)
-
- Preparation methods of tenofovir alafenamide fumarate isomer impurities
-
The invention discloses preparation methods of tenofovir alafenamide fumarate isomer impurities, which comprise preparation methods of four isomer impurities, specifically, preparation methods of 9-{(R)-2-[((R)-{[(R)-1-(isopropoxycarbonyl) ethyl] amino}-phenoxy phosphoryl) methoxy] propyl} adenine, 9-{(R)-2-[((R)-{[(S)-1-(isopropoxycarbonyl) ethyl] amino}-phenoxy phosphoryl) methoxy] propyl} adenine, 9-{(R)-2-[((S)-{[(R)-1-(isopropoxycarbonyl) ethyl] amino}-phenoxy phosphoryl) methoxy] propyl} adenine and 9-{(S)-2-[((R)-{[(R)-1-(isopropoxycarbonyl) ethyl] amino}-phenoxy phosphoryl) methoxy] propyl} adenine. The preparation methods of tenofovir alafenamide fumarate isomer impurities have the beneficial effects that the methods are simple and easy to implement, raw materials are easy to obtain, conditions are mild, cost is low, production is facilitated, and meanwhile the obtained isomer impurity has important significance in preparing high-purity tenofovir alafenamide fumarate.
- -
-
Paragraph 0083; 0084
(2020/07/13)
-
- Preparation method of tenofovir alafenamide
-
The invention discloses a preparation method of tenofovir alafenamide. According to the method, n-butyl acetate is used as a solvent in the synthesis process of an intermediate, namely [[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethyoxyl]methyl]monophenyl ph
- -
-
Paragraph 0021-0023
(2020/11/26)
-
- Tenofovir alafenamide diastereoisomer, preparation method and application of diastereoisomer
-
The invention relates to a tenofovir alafenamide diastereomer as shown in a formula I. The invention also relates to a preparation method of the tenofovir alafenamide diastereoisomer as shown in the formula I, and application of the tenofovir alafenamide diastereomer in detection of purity of the tenofovir alafenamide and salt thereof, detection of content of optical isomers in the tenofovir alafenamide and salt thereof, and quality control in production or preparation of the tenofovir alafenamide and salt thereof. The tenofovir alafenamide diastereomer disclosed by the invention has importantsignificance for quality monitoring and standard research in industrial production of tenofovir alafenamide.
- -
-
Paragraph 0049-0051
(2020/09/16)
-
- Method for synthesizing tenofovir monophenyl ester
-
The invention discloses a method for synthesizing tenofovir monophenyl ester. The method comprises the following steps: adding tenofovir (PMPA), diphenyl iodonium salt, an acid-binding agent and a solvent into a reaction bottle, reacting for a period of time, performing detection, if the solvent is a non-water-soluble solvent, adding diluted hydrochloric acid to adjust the pH value to be below 1 after reaction, layering, adding sodium carbonate into a water layer for neutralization to adjust the pH to 2-3, separating out a solid, and performing filtering. If the solvent is a water-soluble solvent, dichloromethane and diluted hydrochloric acid need to be added to adjust the PH to be below 1, an organic layer is extracted and separated out, sodium carbonate is added to a water layer for neutralization to adjust the pH to 2-3, solid is separated out, filtered and dried, and tenofovir monophenyl ester is obtained. The method has the advantages of being high in yield, easy to operate, few in three wastes and the like.
- -
-
Paragraph 0029-0031
(2020/08/18)
-
- Preparation method of tenofovir alafenamide intermediate
-
The invention relates to a preparation method of a tenofovir alafenol intermediate, which comprises the following steps: (1) reacting PMPA used as a raw material with a first halogenating reagent in afirst reaction solvent to obtain a compound 1; (2) dete
- -
-
Paragraph 0036-0046
(2020/08/18)
-
- Efficient synthesis technology of tenofovir alafenamide
-
The invention discloses an efficient synthesis technology of tenofovir alafenamide. The efficient synthesis technology comprises the steps that A, tenofovir reacts with triphenyl phosphite under an alkali catalysis condition to prepare tenofovir monophenyl ester, wherein the initial reaction temperature is 50-70 DEG C, the reaction temperature rises according to the gradient of 5-10 DEG C/h, and the total reaction duration is 6-10 h; B, the tenofovir monpohenyl ester is subjected to acylating chlorination to prepare tenofovir phenyl ester phosphoryl chloride; C, the tenofovir phenyl ester phosphoryl chloride is isomerized, then the isomerized tenofovir phenyl ester phosphoryl chloride reacts with an L-alanine isopropyl ester compound to prepare a target compound, wherein methylbenzene andother non-polar solvents are adopted for an isomerization solvent. The prepared tenofovir alafenamide has high purity and high yield, the technology operation is simple, the cost is low, complicated technology operation and purification means like using chiral resolution agents are omitted, and the efficient synthesis technology is very suitable for industrial production.
- -
-
Paragraph 0040; 0043-0048
(2019/10/01)
-
- Tenofovir alafenamide hemifumarate preparation method
-
The invention belongs to the technical field of medicines and particularly relates to a tenofovir alafenamide hemifumarate preparation method. The method includes steps: subjecting tenofovir II and triphenyl phosphite to reaction to generate an intermedia
- -
-
Paragraph 0052-0058; 0073-0082
(2019/10/17)
-
- Method for preparing tenofovir alafenamide intermediate
-
The invention discloses a method for preparing a tenofovir alafenamide intermediate, and provides a method for preparing (R)-9-[2-(phosphorylphenol methoxy) propyl] adenine. The method comprises the following steps: condensing (R)-9-[2-(phosphorylphenol methoxy)propyl]propyl and triphenyl phosphite in an organic solvent in the presence of alkali and catalyst to obtain the (R)-9-[2-(phosphorylphenol methoxy) propyl] adenine, wherein the organic solvent is N,N-dimethylacetamide. The preparation method has small solvent dosage and short reaction time; post-treatment is simple and has small catalyst dosage and high yield; and the product has high purity, low production cost and low equipment requirement, and is suitable for industrial production.
- -
-
Paragraph 0035-0037; 0038-0039; 0040-0041; 0042-0049
(2019/07/10)
-
- Method for preparing tenofovir alafenamide intermediate
-
The invention discloses a method for preparing a tenofovir alafenamide intermediate, and provides a method for preparing (R)-9-[2-(phosphorylphenol methoxy) propyl] adenine. The method comprises the following steps: condensing (R)-9-[2-(phosphorylphenol methoxy)propyl]propyl and triphenyl phosphite in an organic solvent in the presence of alkali and catalyst to obtain the (R)-9-[2-(phosphorylphenol methoxy) propyl] adenine, wherein the organic solvent is N-methyl pyrrolidone. The preparation method has small solvent dosage and short reaction time; post-treatment is simple and has small catalyst dosage and high yield; and the product has high purity, low production cost and low equipment requirement, and is suitable for industrial production.
- -
-
Paragraph 0035-0046
(2019/07/10)
-
- Preparation method of (R)-9-[(2-phenoxyphosphonomethoxy)propyl]adenine
-
The invention provides a process for synthesizing tenofovir alafenamide intermediate (R)-9-[(2-phenoxyphosphonomethoxy)propyl]adenine. (R)-9-(2-phosphonomethoxypropyl)adenine is taken as a starting material to carry out a reaction with diphenyl phosphite
- -
-
Paragraph 0092; 0093
(2019/10/17)
-
- A method for preparing for fuwei ira phenol amine intermediate
-
The invention discloses a key intermediate for the fuwei ira phenol amine PMPA single phenyl ester preparation method. It is will be PMPA, triphenyl phosphate and organic alkali mixing, in the absence of solvent the heating reaction preparation PMPA singl
- -
-
Paragraph 0018-0025
(2019/07/04)
-
- Method for preparing tenofovir alafenamide fumarate key intermediate phenyl PMPA
-
The invention belongs to the technical field of medicine, and provides a method for preparing a tenofovir alafenamide fumarate key intermediate phenyl PMPA. The method comprises the steps that tenofovir is used as a raw material and reacted with an esterification reagent to obtain phenyl PMPA, wherein the esterification reagent is prepared from a catalyst, a dehydrating agent, an organic base andphenol, and the reaction is carried out in an organic solvent at a reaction temperature of 80-120 DEG C. According to the technical scheme, the problem that a method for preparing the tenofovir alafenamide fumarate key intermediate phenyl PMPA in the prior art is long in reaction time and low in product purity is solved.
- -
-
Paragraph 0059-0062; 0065-0067
(2019/11/13)
-
- Preparation method and application of process impurity of tenofovir alafenamide fumarate
-
The present invention relates to a process impurity of tenofovir levamide amine fumarate 9-[(R)-2-[[(S)-[[(S)-1-(isopropoxycarbonyl)ethyl]amino]phenoxyphosphinyl]methoxy]propyl]adenine hemifumarate, and a preparation method thereof. The impurity is select
- -
-
Paragraph 0117; 0118; 0119
(2019/10/01)
-
- A TAF nucleoside derivatives and intermediates thereof
-
The invention discloses a preparation method of a TAF (tenofovir alafenamide fumarate) nucleoside derivative and an intermediate of the TAF nucleoside derivative. The method comprises the steps that in a solvent of a compound II, in the presence of alkali, stirring is performed until the reaction is completed, and a required compound I is obtained. Compared with the prior art, the preparation method has the advantages that the raw materials are cheap and are easily obtained; the reaction conditions are mild; the side reactions are few; the yield is high; the environment pollution is little; the preparation method is applicable to industrial production; a new path is provided for the preparation of the TAF key intermediate. The formulas are shown in the specification.
- -
-
Paragraph 0046; 0047; 0048
(2019/05/19)
-
- Novel tenofovir prodrug purifying method
-
The invention relates to a novel tenofovir prodrug purifying method. The method specifically includes performing recrystallization on tenofovir prodrug shown as a formula Ia1 in acetonitrile or a mixed solvent of acetonitrile and aromatic hydrocarbon solvent or a mixed solvent of an acetonitrile and ether solvent so that the tenofovir prodrug shown as the formula Ia1 and with optical purity of 99.8% or more can be prepared. The tenofovir prodrug is shown as the formula Ia1.
- -
-
-
- Novel antiviral nucleoside reverse transcriptase inhibitor
-
The invention relates to a novel antiviral nucleoside reverse transcriptase inhibitor compound, a pharmaceutical composition comprising the same and preparation and application thereof. Particularly,the invention discloses a condensed pyrimidine compound
- -
-
Paragraph 0331; 0333; 0334; 0335; 0336
(2019/04/06)
-
- NUCLEOSIDE PHOSPHATE COMPOUND AND PREPARATION METHOD AND USE THEREOF
-
Provided in the present invention are a compound of Formula (I), a pharmaceutical composition comprising the same, a method for preparing the same, and use thereof as a NS5B polymerase inhibitor, a DNA polymerase inhibitor or a reverse transcriptase inhibitor for the prevention or treatment of viral diseases or cancers.
- -
-
Paragraph 0194-0195
(2019/11/14)
-
- Preparation method of key intermediate of tenofovir alafenamide hemifumarate
-
The invention discloses a preparation method of a key intermediate of tenofovir alafenamide hemifumarate-monophenyl PMPA, which comprises the following steps: (1) preparing a dihalogenated compound represented by Formula II from the PMPA represented by Fo
- -
-
Paragraph 0049; 0052; 0053; 0058; 0059; 0061; 0064; 0065
(2019/10/17)
-
- (R)-9 - [2 - (phosphorothio phenol ylmethoxy) propyl] adenine preparation method
-
The invention discloses a preparation method of (R)-9-[2-(phosphoryl phenol methoxyl)propyl]adenine. The preparation method comprises the following steps: adding (R)-9-[2-(phosphoryl methoxy) propyl] adenine represented by the formula (I) into a solvent,
- -
-
Paragraph 0040; 0062-0064; 0074; 0085; 0089
(2018/11/03)
-
- Tenofovir prodrug or pharmaceutical salts and application thereof in medicines
-
The invention relates to tenofovir prodrug and application thereof in medicines. Specifically, the invention relates to a compound shown as general formula (I) or general formula (II), or isomers andpharmaceutical salts thereof, and application in preparation of drugs for treatment of viral infectious diseases, especially (HIV) infection, hepatitis B and hepatitis B virus induced diseases. Specifically, definitions of the substituent groups in the general formula (I) or general formula (II) are identical to those in the specification.
- -
-
Paragraph 0021-0022
(2018/06/26)
-
- Simple synthesizing process for tenofovir alafenamide fumarate
-
The invention discloses a simple synthesizing process for tenofovir alafenamide fumarate. According to the simple synthesizing process for the tenofovir alafenamide fumarate, a target product, namely,tenofovir alafenamide fumarate, is synthesized by taking tenofovir as a raw material through four steps of esterifying by using triphenyl phosphite, amidating by using L-alanine isopropyl ester hydrochloride, regulating pH by using phenol and DBU for resolving, and salifying by using fumaric acid. The process is simple and low in reaction temperature, and is more suitable for industrialization.
- -
-
Paragraph 0036; 0039; 0040
(2018/09/11)
-
- Preparation method of tenofovir alafenamide hemifumarate
-
The invention discloses a preparation method of tenofovir alafenamide hemifumarate. The preparation method comprises the following steps of: reacting tenofovir with triphenyl phosphite under the condition of alkali catalysis to prepare tenofovir phenol ester; preparing tenofovir alafenamide through acylating chlorination and a reaction with L-alanine isopropyl ester; preparing tenofovir alafenamide hemifumarate by a special salt-forming process with fumaric acid. The tenofovir alafenamide hemifumarate prepared by the process is accurate in control of a salt type ratio, and simple in process operation, and avoids complex process operation and purification means such as chiral resolution, the total purity can reach 99% or more, and indexes of related substances are qualified.
- -
-
Paragraph 0008; 0037-0039
(2018/03/25)
-
- Preparation method of fumaric acid tenofovir alafenamide
-
The invention provides a preparation method of fumaric acid tenofovir alafenamide. By esterification reaction, halogenating reaction, condensation reaction, refining and salt forming reaction, the fumaric acid tenofovir alafenamide which is high in yield, easy to purify and suitable for industrial mass production is obtained.
- -
-
Paragraph 0069; 0071
(2018/09/11)
-
- A key intermediate for the preparation of fumaric acid for fuwei ira phenol amine (by machine translation)
-
The invention the invention belongs to the field of drug synthesis, relates to a pharmaceutical intermediates, in particular to a method for the preparation of a key intermediate in the fumaric acid for fuwei ira phenol amine. The present invention provid
- -
-
Paragraph 0045; 0051; 0052; 0053
(2018/11/27)
-
- Efficient synthesis and resolution of tenofovir alafenamide
-
Background: Tenofovir alafenamide (TAF) is an oral antiviral prodrug of tenofovir (TFV), we have developed a facial and efficient method for the synthesis and chiral resolution of TAF. Method: The practical synthetic route of a mixed two diastereomers at phosphorous could start from (R)-9-[2-(Phosphonomethoxy)propyl]adenine (PMPA), the esterification reaction between PMPA and phenol occurred under the catalysis of dicyclohexylcarbodiimide (DCC) in 1-methyl-2-pyrrolidinone (NMP) at the temperature of 100o C to afforded 1. Phosphonochloridate was synthesized from 1 by chloride acetylation with thionyl chloride, and then react with an excess of L-Alanine isopropyl ester hydrochloride to give the diastereomer mixture of 9-[(R)-2-[[(R,S)-[[(S)-1-(isopropoxycarbonyl)ethyl] amino]-phenoxyphosphinyl]methoxy]propyl]adenine (2). The antipodes of 2 were separated in a satis-factory yield and diastereomeric excess (99% de) by resolution via formation diastereoisomer salt or inclusion complex to afford the more potent diastereomer (3). Tenofovir Alafenamide hemifumarate could be afforded by 3 and fumaric acid in a 1:0.5 ratio. Results: The diastereomeric excess of 3 could reach to 99% de. Conclusion: In a word, we have developed an efficient and chromatography-free route for the prepara-tion of TAF. In consideration of the expensive equipment and higher operation cost of SMBC, we chose a traditional resolution route to obtain chiral phosphorus.
- Gan, Yongjun,Ran, Kerui,Xie, Hongmeng,Yang, Bin
-
-
- COMBINATION THERAPY COMPRISING TENOFOVIR ALAFENAMIDE HEMIFUMARATE AND COBICISTAT FOR USE IN THE TREATMENT OF VIRAL INFECTIONS
-
The use of the hemifumarate form of {9-[(R)-2-[[(S)-[[(S)-1-(isopropoxycarbonyl)ethyl]amino]phenoxyphosphinyl]methoxy]propyl]adenine} (tenofovir alafenamide hemifumarate) in combination with cobicistat is disclosed. In addition, the combination of tenofovir alafenamide hemifumarate, cobicistat, emtricitabine, and elvitegravir, and the combination of tenofovir alafenamide hemifumarate, cobicistat, emtricitabine, and darunavir, are disclosed.
- -
-
Paragraph 0304
(2017/08/01)
-
- Nucleoside phosphoramidate type compound with HBV/HIV resistance activity and salt and application of nucleoside phosphoramidate type compound
-
The invention relates to a nucleoside phosphoramidate type compound with HBV/HIV resistance activity, an isomer of the nucleoside phosphoramidate type compound, pharmaceutically-acceptable salt of the nucleoside phosphoramidate type compound, a solvate or crystal of the nucleoside phosphoramidate type compound, a medicine composition of the nucleoside phosphoramidate type compound, and application of the nucleoside phosphoramidate type compound. According to related novel non-cyclic nucleoside phosphoramidate, on the phosphoramidate part, amino acid is D-amino-acid. D-amino-acid ester is introduced in the prodrug, and a new non-cyclic nucleotide amide compound which has higher chemical stability, higher lipid solubility and higher virus inhibition activity is expected to be obtained. By means of the creative design, the virus resistance activity of medicine is improved, solubility and pharmacokinetics characteristics of the medicine are improved, the concentration ratio in tissue cells and plasma is increased, and therefore the curative effect, safety and tolerance of the medicine can be improved, and very good clinical application prospects are achieved.
- -
-
Paragraph 0031
(2017/08/28)
-
- Tenofovir alafenamide hemifumarate novel crystal form
-
The invention discloses a tenofovir alafenamide hemifumarate, ((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxyl)methyl(phenoxyl) phosphono)-L-alanine isopropyl hemifumarate, novel crystal form (crystal form B), drug preparations containing the tenofovir alafenamide hemifumarate novel crystal, and treatment applications and preparation methods of the tenofovir alafenamide hemifumarate novel crystal. The tenofovir alafenamide hemifumarate novel crystal is stable at high temperature high moisture conditions; large-scale preparation is convenient to realize; and application prospect is promising.
- -
-
Paragraph 0028; 0029
(2018/03/24)
-
- Aryl substituted phosphorothio amine derivatives and their use in medical application
-
The invention relates to an aryl-substituted phosphonaminate and an application of the aryl-substituted phosphonaminate in medical science, in particular to an aryl-substituted phosphonaminate showed in a general formula (I), stereoisomer of the aryl-subs
- -
-
Paragraph 0111-0114
(2017/09/12)
-
- Substituted amino acid thioester compound, its composition and application specifically related to preparing the drugs for treating virus infectious diseases
-
The present invention relates to a substituted amino acid thioester compound represented by the general formula (A), its composition and application, wherein the definitions of the substituents in the general formula (A) are the same as those defined in t
- -
-
Page/Page column 24; 25; 26
(2017/10/26)
-
- Phosphonate prodrug of adenine derivative and medical application of phosphonate prodrug
-
The invention relates to a phosphonate prodrug of an adenine derivative and medical application of the phosphonate prodrug. Specifically, the invention relates to a compound shown in a general formula (I) or an optical isomer, or a pharmaceutical salt, or
- -
-
Paragraph 0018; 0021; 0046; 0052; 0058
(2017/08/28)
-
- Industrialized continuous production method of hemifumarate tenofovir alafenamide
-
The invention discloses an industrialized continuous production method of tenofovir alafenamide and hemifumarate. The method comprises the following steps: firstly, in the presence of an acid-binding agent, reacting tenofovir with triphenyl phosphate to obtain a TAF-I M shown as a formula II; secondly, continuously preparing a TAF-II M by using the TAF-I M; thirdly, carrying out a salt forming reaction on the TAF-II M to obtain the hemifumarate tenofovir alafenamide. According to the industrialized continuous production method disclosed by the invention, a key compound tenofovir alafenamide is obtained by continuous production; the hemifumarate tenofovir alafenamide is obtained by accurately feeding fumaric acid and the tenofovir alafenamide; and in addition, a diastereoisomer of the tenofovir alafenamide is inhibited by using high catalytic enantioselectivity of a proline catalyst, and industrial production of optically-pure tenofovir alafenamide of which the purity is greater than 99.9 percent is realized by primary crystallization. The industrial production method disclosed by the invention has the advantages of simplicity, safety and low production cost; and besides, a high-purity product is obtained.
- -
-
Paragraph 0056; 0069; 0070; 0071
(2018/01/19)
-
- Phosphamide derivative substituted by aryl group and medical applications thereof including a use in manufacturing drugs for treating virus infectious diseases
-
The present inventions relates to a phosphamide derivative substituted by an aryl group and medical applications thereof, which specifically relates to the phosphamide derivative substituted by an aryl group, stereoisomers thereof or the pharmaceutically
- -
-
Page/Page column 20
(2017/10/14)
-
- Preparation method of TAF (Tumor Angiogenesis Factor) nucleoside derivative
-
The invention discloses a preparation method of a TAF (Tumor Angiogenesis Factor) nucleoside derivative. The method comprises the following steps: adding a compound II into alkali and a catalyst in a solvent, and stirring till the reaction is complete, thus obtaining a compound I. Compared with the prior art, raw materials used in the preparation method are readily available, reaction conditions are mild, little side effects are caused, the yield is high, the environmental pollution is low, and the preparation method is suitable for industrial production; a new way is provided for preparation of a fumarate tenofurol phenolamine key midbody.
- -
-
Paragraph 0059-0060
(2017/09/28)
-
- A prodrug for fuwei purification method
-
The invention relates to a method for purifying a tenofovir prodrug. Specifically, the method utilizes D-(+)-dibenzoyl tartaric acid salifying and crystallization as well as subsequent alkali neutralization to separate and purify the mixture of a compound represented by a general formula I and the compound represented by a general formula II, thereby preparing the compound represented by the general formula I with a purity of over 95%. (The general formulas I and II are shown in the description).
- -
-
-
- Phosphoric acid ester preparation method
-
The invention relates to a phosphoric acid ester preparation method, and belongs to the technical field of pharmacy. According to the present invention, a raw material, phenol and an alkali are subjected to water separation treatment under a certain condition, thionyl chloride is added, a reaction is performed, and post-treatment is performed to obtain the high-yield high-quality product; and the operation of the method is simple, the reaction post-treatment is smooth, the solvent is easy to recover, and the method is suitable for industrial production.
- -
-
Paragraph 0053; 0054; 0056; 0058
(2018/04/02)
-
- Phosphoric ester preparation method
-
The invention relates to a phosphoric ester preparation method, and belongs to the technical field of pharmacy. According to the present invention, a raw material and a reaction solvent are mixed, the obtained mixture is optionally subjected to reflux and water separation treatment, and the obtained product, phenol, DMF, thionyl chloride and an alkali reagent are subjected to a reaction under a certain condition so as to obtain the high-yield product; and the method has the easy operation, and can be used for industrial production.
- -
-
Paragraph 0044; 0047; 0050; 0053; 0056; 0059; 0061-0063
(2018/04/02)
-
- Preparation method and application for high-purity tenofovir alafenamide fumarate intermediate
-
The invention discloses a preparation method and an application for a high-purity tenofovir alafenamide fumarate intermediate. The preparation method for the tenofovir alafenamide fumarate intermediate namely tenofovir alafenamide II provided by the invention comprises the following steps: subjecting crude tenofovir alafenamide fumarate intermediate namely tenofovir alafenamide II to recrystallization in a mixed solvent of a nitrile solvent and water or a mixed solvent of the nitrile solvent and an aromatic hydrocarbon solvent so as to obtain the high-purity tenofovir alafenamide fumarate intermediate namely tenofovir alafenamide II. The high-purity tenofovir alafenamide II has an optical purity larger than 99.50% and a chemical purity larger than 99.60%; and the crude tenofovir alafenamide fumarate intermediate namely tenofovir alafenamide II has the optical purity in a range of 60.00% to 99.00% and the chemical purity in a range of 60.00% to 99.00%. The preparation method provided by the invention has the advantages of simple and safe operation, high yield, high product purity, low production cost, and applicability to industrial production.
- -
-
Paragraph 0041; 0042; 0043
(2017/08/28)
-
- Phosphamide nucleosides compound, pharmaceutically acceptable salt and application thereof, and pharmaceutical composition
-
The invention provides a phosphamide nucleosides compound as shown in a formula (I). Compared with the prior art, the phosphamide nucleosides compound has the advantages that the phosphamide nucleosides compound has antiviral activity which is remarkably higher than that of TAF on aspects of HIV resisting and hepatitis B resisting; the HIV resisting activity of some compounds is about 10 times higher than that of the TAF, and the hepatitis B resisting activity of the same compounds is also 2-5 times higher than that of the TAF; moreover, the phosphamide nucleosides compound has stable chemical properties and is difficult to hydrolyze by hydrolytic enzymes; compared with the TAF, the phosphamide nucleosides compound has superiority on aspect of toxicity and especially renal toxicity, and patients suffering from HIV and/or HBV can be effectively treated by the compound or isomer thereof at a low clinic dosage.
- -
-
Paragraph 0080; 0081; 0082; 0083; 0084
(2017/08/28)
-
- AN IMPROVED PROCESS FOR THE PREPARATION OF TENOFOVIR ALAFENAMIDE OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
-
The present invention generally relates to an improved process for the preparation of tenofovir alafenamide or pharmaceutically acceptable salts thereof and preparation thereof. The present invention also relates to crystalline forms of monophenyl PMPA, an important intermediate of tenofovir alafenamide, and their preparation.
- -
-
Page/Page column 30; 31; 33; 34
(2018/04/12)
-
- Acyclic nucleoside phosphamide D-amino-acid ester derivative, preparation method of derivative salt and application of derivative to antiviral effect
-
The invention belongs to the field of medical chemical antiviral effects, and relates to an acyclic nucleoside phosphamide D-amino-acid ester derivative, a preparation method of derivative salt and an application of the derivative to the antiviral effects. The invention further provides a compound comprising the derivative, a stereoisomer of the derivative, pharmaceutically acceptable salt, a hydrate, a solvate or crystal and drug combination and an application of the compound or combination to treatment and/or prevention of Aids and hepatitis B virus infection. The in vivo activity of the compound is remarkably superior to that of a pro-drug of acyclic nucleoside phosphamide L-amino-acid ester, and the compound has obvious clinical application values.
- -
-
Paragraph 0062; 0063; 0064
(2017/03/22)
-
- PHOSPHORIC ACID/PHOSPHONIC ACID DERIVATIVES AND MEDICINAL USES THEREOF
-
The present invention relates to phosphoric acid/phosphonic acid derivatives shown by formula (I), wherein, R 1 or R 2 represents the following structures: (Q1), or (Q2), or (Q3). Q1 represents ester derivatives of L-amino acid, wherein R 3 is alkyl with
- -
-
Paragraph 0063-0065
(2016/11/02)
-
- NUCLEOSIDE KINASE BYPASS COMPOSITIONS AND METHODS
-
The present invention relates to disulfide masked prodrug compounds, compositions and methods that are amenable to bioactivation by a reducing agent such as glutathione. Such disulfide based compounds, compositions, and methods can be useful, for example, in providing novel prodrugs for use as therapeutics.
- -
-
Paragraph 0163
(2015/11/24)
-